Germline Genetic Testing of the TP53 Gene

Germline Genetic Testing of the TP53 Gene: Identification, Characterization, and Management of Patients and Families at High Risk of Cancer

This is a retrospective, observational, single-center study designed as a cohort analysis. The study population will include consecutive patients referred for genetic counseling and TP53 germline genetic testing between 2004 and 2025 at the Division of Cancer Prevention and Genetics of the IEO. The primary endpoint is to determine the overall detection rate of Pathological Variants (PVs) in the TP53 gene among individuals referred to the institute and the differences between the groups.

Study Overview

• Status: Recruiting
• Conditions: TP53 Gene Mutation; TP53 Gene Germline Mutation Carrier; Multi-Gene Transcriptional Profiling

• Study Type: Observational
• Enrollment (Estimated): 1940

Contacts and Locations

• Study Contact: Name: Mariarosaria Calvello, MD; Phone Number: +39 0294372651; Email: mariarosaria.calvello@ieo.it

Study Locations

• Italy
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo di Oncologia
    • Contact: Mariarosaria Calvello; Phone Number: +39 0294372651; Email: mariarosaria.calvello@ieo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a retrospective, observational, single-center study designed as a cohort analysis. The study population will include consecutive patients referred for genetic counseling and TP53 germline genetic testing between 2004 and 2025 at the Division of Cancer Prevention and Genetics of the IEO.

Participants will be stratified according to the referral criteria for genetic counseling and testing or the approach used.

Description

Inclusion Criteria:

• Have undergone at least one genetic counseling session at the Division of Cancer Prevention and Genetics of the IEO;
• Have undergone germline TP53 genetic testing, regardless of the referral criteria for counseling and/or testing or the approach used;
• Have provided written informed consent for participation in scientific research.

Exclusion Criteria:

• Absence of signed informed consent for participation in scientific research.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; Individuals fulfilling the 2015 Chompret criteria.
Group 2; Individuals fulfilling the Li-Fraumeni-Like (LFL) criteria according to Birch or Eeles.
Group 3; Individuals undergoing Multi-Gene Transcriptional Profiling in the absence of Li-Fraumeni Sindrome/Li-Fraumeni-Like criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall detection rate of Pathological Variants (PVs) in the TP53 gene.	To determine the overall detection rate of PVs in the TP53 gene among individuals referred to the Division of Cancer Prevention and Genetics at the IEO for TP53 genetic testing. Detection rate calculated as the number of patients with mutation of the TP53 gene divided by the total numer of patients tested.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate of pathological variants in the TP53 gene across cohort	Fisher's exact test or Chi-squared test will be applied, as appropriate, to compare the detection rate of pathological variants in the TP53 gene between different groups.	Baseline
Detection rate of Variant of Uncertain Significance in the TP53 gene.	To determine the detection rate of Variant of Uncertain Significance (VUS) in the TP53 gene among all groups. Detection rate calculated as the number of patients with Variant of Uncertain Significance of the TP53 gene divided by the total numer of patients tested. Evaluation for potential reclassification of the detected TP53 VUS according to the 2025 ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Guidelines (v2.3.0)	Baseline
Detection rate of pathological variants and variants of Uncertain Significance in other cancer susceptibility genes.	Detection rate calculated as the number of patients with a mutation of gene other than the TP53 gene divided by the total numer of patients tested.	Baseline
Disease Free Survival	To compare the Disease Free Survival l of breast cancer patients carrying pathological variants in the TP53 gene with those observed in breast cancer patients tested through Multigene Panel Testing and who did not carry pathological variants or Variants of Uncertain Significance in any of the tested genes. Disease Free Survival will be defined as the time from surgery to invasive loco-regional recurrence, metastasis, other primary non-breast carcinomas, or death from any cause, whichever occurs first.	5 years
Overall Survival (OS)	To compare the Overall Survival of breast cancer patients carrying pathological variants in the TP53 gene with those observed in breast cancer patients tested through Multigene Panel Testing and who did not carry pathological variants or Variants of Uncertain Significance in any of the tested genes. OS will be defined as the time from surgery to death from any cause.	5 years

Collaborators and Investigators

• Sponsor: European Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: UID 5143; L2-483 (Other Identifier: Comitato Etico Territoriale Lombardia 2)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No